Individualized Dosimetry for Holmium-166 Radioembolization in Patients With Unresectable Hepatocellular Carcinoma

Inclusion Criteria:

1. Provided written informed consent.
2. Female or male aged 18 years and over.
3. Diagnosis of HCC established according to AASLD criteria: nodule >1 cm in a patient atrisk for HCC, with combination of arterial hypervascularity and venous or delayedphase wash-out on multiphase CT-scan or MRI-scan. LR-5 and LR- 4 based on LiverImaging Reporting and Data System can be included.
4. No curative treatment options (resection, transplant, or in case of solitary tumour,RFA).
5. Life expectancy of at least 6 months.
6. ECOG Performance status 0-1.
7. Liver-dominant disease (maximum 5 lung nodules all ≤1.0 cm, solitary clinically stableadrenal metastasis, and mesenteric or portal lymph nodes all ≤2.0 cm are accepted).
8. Child-Pugh class A5-6 or B7.
9. At least one measurable liver lesion according to the modified RECIST criteria.
10. Negative pregnancy test for women of childbearing potential. Female patients ofchildbearing potential should use a highly effective acceptable method ofcontraception (oral contraceptives, barrier methods, approved contraceptive implant,long-term injectable contraception, intrauterine device or tubal ligation) or shouldbe more than 1 year postmenopausal or surgically sterile during their participation inthis study (from the time they sign the consent form), to prevent pregnancy.

Exclusion Criteria:

1. Evidence of significant extrahepatic disease (MRI-scan liver and multiphase abdominalCT as well as a thoracic CT are routinely performed at screening).
2. Hepatic radiation therapy within the last 4 weeks before the start of study therapy.
3. Previous or current treatment with RE. Previous treatment with TACE, surgery, RFA, andprevious or current treatment with systemic treatment are allowed.
4. Major surgery within 4 weeks or incompletely healed surgical incision before startingstudy therapy.
5. Serum bilirubin > 34 umol/L in the absence of a reversible cause
6. Glomerular filtration rate <35 ml/min.
7. Non-correctable INR >1.5 in case of femoral approach (as opposed to radial).
8. Platelet count <50 109/l.
9. Significant cardiac event (e.g., myocardial infarction, superior vena cava (SVC)syndrome, New York Heart Association (NYHA) classification of heart disease ≥2) within 3 months before entry, or presence of cardiac disease that in the opinion of theinvestigator increases the risk of ventricular arrhythmia.
10. Pregnancy or breastfeeding.
11. Patients suffering from psychic disorders that make a comprehensive judgmentimpossible, such as psychosis, hallucinations and/or depression.
12. Patients who are declared incapacitated.
13. Previous enrolment in the present study.
14. Male patients who are not surgically sterile or do not use an acceptable method ofcontraception during their participation in this study (from the time they sign theconsent form), to prevent pregnancy in a partner.
15. Evidence of untreated, clinically significant grade 3 portal hypertension (i.e. largevarices at oesophagi-gastro-duodenoscopy). In these cases, therapy with non-selectivebeta-blocker (propranolol) or rubber band ligation should be instituted according toaccepted guidelines. In case of small varices, prophylactic propranolol is advised.
16. Portal vein thrombosis (tumour and/or bland) of the main branch (diagnosed on contrastenhanced transaxial images). Involvement of the right or left portal vein branches andmore distal is accepted.
17. Untreated active hepatitis. In case of detectable viral HBV load, appropriatetreatment should be instituted.
18. Transjugular intrahepatic portosystemic shunt (TIPS).
19. Body weight over 150 kg (because of maximum table load).
20. Severe allergy for intravenous contrast used (Visipaque®)
21. Lung shunt >30 Gy, as calculated using scout dose SPECT/CT.
22. Extrahepatic deposition of scout dose activity. Activity in the falciform ligament,portal lymph nodes and gallbladder is accepted.